beta catenin
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Function
- role in the regulation of cell adhesion & in signal transduction through the Wnt pathway
- two separate pools are found in the cytoplasm:
- one is PSEN1/cadherin/catenin complex which anchors to the actin cytoskeleton
- the other pool is part of a large complex containing AXIN1, AXIN2, APC, CSNK1A1 & GSK3B that promotes phosphorylation on N-terminal Ser & Thr residues & ubiquitination of CTNNB1 via BTRC & its subsequent degradation by the proteasome
- Wnt-dependent activation of DVL antagonizes the action of GSK3B
- when GSK3B activity is inhibited the complex dissociates, CTNNB1 is dephosphorylated & is no longer targeted for destruction
- the stabilized protein translocates to the nucleus, where it binds TCF/LEF-1 family members, TBP, BCL9 & possibly also RUVBL1 & DUPLIN
- binds CTNNBIP & EP300
- CTNNB1 forms a ternary complex with LEF1 & EP300 that is disrupted by CTNNBIP1 binding
- interacts with the PDZ domain of TAX1BP3; this interaction inhibits the transcriptional activity of CTNNB1
- interacts with AJAP1, BAIAP1, CARM1, CTNNA3, CXADR & PCDH11Y.
- binds SLC9A3R1
- interacts with GLIS2 & MUC1 interacts with SLC30A9
- interacts with XIRP1 (putative)
- phosphorylation by GSK3B requires prior phosphorylation of Ser-45 by another kinase (CKIa phosphorylates beta-catenin on Ser-45)
- phosphorylation proceeds then from Thr-41 to Ser-37 & Ser-33
- EGF stimulates tyrosine phosphorylation
- phosphorylation on Tyr-654 decreases CDH1 binding & enhances TBP binding
- ubiquitinated by a E3 ubiquitin ligase complex containing UBE2D1, SIAH1, CACYBP/SIP, SKP1A, APC & TBL1X (probable)
- ubiquitination leads to its subsequent proteasomal degradation
Structure
- belongs to the beta-catenin family
- contains 12 ARM repeats
Compartment
- cytoplasm, nucleus
- cytoplasmic when it is unstabilized (high level of phosphorylation) or bound to CDH1
- translocates to the nucleus when it is stabilized (low level of phosphorylation)
- interaction with GLIS2 & MUC1 promotes nuclear translocation
Alternative splicing
named isoforms=2
Expression
- expressed in several hair follicle cell types: basal & peripheral matrix cells, & cells of the outer and inner root sheats.
- expressed in colon
Pathology
- activating mutations in CTNNB1 have oncogenic activity resulting in tumor development
- somatic mutations are found in various tumor types, including colon cancers, ovarian cancer & prostate carcinomas, hepatoblastoma, hepatocellular carcinoma
- defects in CTNNB1 are a cause of
- chromosomal translocation t(3;8)(p21;q12) involving CTNNB1 with PLAG1 may be a cause of salivary gland pleiomorphic adenomas
- mutations &/or accumulation of beta catenin seen in some dedifferentiated liposarcomas & malignant fibrous histiocytomas
Laboratory
More general terms
References
- ↑ Liu C, Li Y, Semenov M, Han C, Baeg GH, Tan Y, Zhang Z, Lin X, He X. Control of beta-catenin phosphorylation/degradation by a dual-kinase mechanism. Cell. 2002 Mar 22;108(6):837-47. PMID: https://www.ncbi.nlm.nih.gov/pubmed/11955436
- ↑ UniProt http://www.uniprot.org/uniprot/P35222.html
- ↑ Sakamoto A, Oda Y, Adachi T, Saito T, Tamiya S, Iwamoto Y, Tsuneyoshi M. Beta-catenin accumulation and gene mutation in exon 3 in dedifferentiated liposarcoma and malignant fibrous histiocytoma. Arch Pathol Lab Med. 2002 Sep;126(9):1071-8. PMID: https://www.ncbi.nlm.nih.gov/pubmed/12204056
- ↑ Atlas of genetics & cytogenetics in oncology & Haematology http://atlasgeneticsoncology.org/genes/CTNNB1ID71.html
- ↑ Wikipedia, beta-catenin entry http://en.wikipedia.org/wiki/beta-catenin
Database
- UniProt: http://www.uniprot.org/uniprot/P35222.html
- Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:1499
- OMIM: https://mirror.omim.org/entry/116806
- OMIM: https://mirror.omim.org/entry/132600
- OMIM: https://mirror.omim.org/entry/155255
- Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=1499